Multimorbidity, the coexistence of multiple chronic conditions, poses a major and growing challenge to aging adults, their families, and healthcare systems. Most older adults have multiple chronic conditions that interact to profoundly affect physical functioning and health-related quality of life. Despite this, critical gaps remain in the measurement of multimorbidity. In particular, there are few practical tools to guide clinicians, researchers, and policymakers who seek to improve the care for older adults. Current measures for multimorbidity have used mortality, healthcare cost, and utilization, but have not focused on patient-centered outcomes to quantify burden of disease. Statistical limitations in traditional methods to measure disease interactions beyond simple two-way disease interactions have also hampered our epidemiologic understanding of multimorbidity and its full impact on health and functional outcomes. To bridge these gaps, this proposal aims to 1) Develop and validate a new multimorbidity index for use in ICD-coded conditions; 2) Refine the multimorbidity index by incorporating multiple-order disease interactions and determine the incremental value of their inclusion; and 3) Assess the utility of the multimorbidity index through its association with key functional outcomes including physical and cognitive performance, basic and instrumental activities of daily living, depression, and mortality. The proposed studies will use unique data linkages between patient-reported outcomes in the nationally- representative Health and Retirement Study and Medicare claims to develop and internally validate a multimorbidity index for International Classification of Diseases (ICD)-coded chronic conditions weighted to physical functioning. Novel approaches to data shrinkage techniques will be used to select significant interactions among multiple potential disease combinations associated with physical functioning. The utility of the multimorbidity index will be assessed through its prospective associations with physical and cognitive performance, basic and instrumental activities of daily living, and mortality. The successful completion of these studies will yield a validated multimorbidity measure that captures the impact of coexisting chronic diseases on physical functioning in older adults relevant for clinical care, research, and policy. Through this award, the candidate will achieve immediate career goals to gain new specialized skills in using administrative claims, ICD coded data, and novel statistical approaches to high-dimension data, and achieve a deeper understanding of measuring key health outcomes in older adults with multimorbidity. The facilities, sponsoring department, and intellectual resources at the University of Michigan provide an exceptional milieu for this career development award and Early Stage Investigator. The training and professional development acquired through this award will contribute to the candidate's long-term goal to be an independent clinician- investigator focused on improving the management, quality of care, and prognosis of vulnerable older adults with multimorbidity.